This Mentored Research Scientist Development Award (K01) application is designed to reorient the applicant's research career from behavioral medicine to psychiatric genetics with a focus on Borderline Personality Disorder (BPD). BPD is a complex phenotype characterized by affeetive instability, impaired social relationships and impulsivity. Progress in understanding the neurogenetics of BPD has been slowed by the fact that the disorder is clinically heterogeneous and likely shows complex inheritance, influenced by the interaction of multiple genetic and environmental factors. These conditions suggest that classic genetic approaches, such as standard affected/unaffected linkage analysis and candidate gene studies, are unlikely to be the optimal approaches for identifying genetic factors associated with the disorder. Reconceptualizing the categorical disorder into more specific, dimensional phenotypes (i.e., intermediate phenotypes) that are putatively closer to the neuropathology of the disorder might increase the likelihood of identifying genetic factors. Impulsivity and impulsive aggression have been identified as core features of the disorder. This application proposes to evaluate impulsivity as a model intermediate phenotype for BPD using a variety of measures (e.g., clinical interview, self-report, behavior in laboratory tasks) administered to a large sample of adults who are not selected for BPD; and to people who meet DSM-IV diagnostic criteria for BPD. Siblings of BPD probands and matched controls will also complete self-report measures of impulsivity, aggression, and affective instability. The candidate will complete didactic training in genetic epidemiology/psychiatric genetics and the research plan will be conducted in the context of funded, ongoing research programs at Mount Sinai School of Medicine and the University of Pittsburgh. This research will evaluate whether the structure of impulsivity is similar in normative and patient samples and which aspects of impulsivity (e.g., nonplanning, novelty seeking) are associated with aggression and behavioral task performance in the normative sample and in people with BPD. This work will also examine familial aggregation of impulsivity, aggression and affective instability in preparation for submission of a collaborative R01 application to conduct joint linkage analysis of BPD and BPD endophenotypes in extended pedigrees.